title: Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with pazopanib after disease progression with other targeted therapies.
abstract: OBJECTIVE
  The multi-tyrosine kinase inhibitor pazopanib prolongs progression-free survival (PFS) versus placebo in treatment-naive and cytokine-refractory metastatic clear-cell renal cell carcinoma (ccRCC). Outcomes and safety data with pazopanib after targeted therapy (TT) are limited.
  
  
  METHODS
  We retrospectively evaluated records of consecutive patients with metastatic ccRCC who had progressive disease (PD) after TT and received pazopanib from November 2009 through November 2011. Tumour response was assessed by a blinded radiologist using Response Evaluation Criteria In Solid Tumours (RECIST). PFS and overall survival (OS) were estimated by Kaplan-Meier methods.
  
  
  RESULTS
  Ninety-three patients were identified. Median number of prior TTs was 2 (range, 1-5). There were 68 events (PD or death). Among 85 evaluable patients, 13 (15%) had a partial response. Median PFS was 6.5 months (95% CI: 4.5-9.7); median OS was 18.1 months (95% CI: 10.26-NA). Common adverse events (AEs) included fatigue (44%), elevated transaminases (35%), diarrhoea (30%), hypothyroidism (18%), nausea/vomiting (17%), anorexia (14%) and hypertension exacerbation (14%); 91% of AEs were grade 1/2. Eleven patients (12%) discontinued therapy due to AEs. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  Pazopanib demonstrated efficacy in patients with metastatic ccRCC after PD with other TTs. Toxicity overall was mild/moderate and manageable.
authors.affiliation: Hematology and Medical Oncology Fellowship Program, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Matrana
authors.forename: C
authors.initials: C
authors.lastname: Duran
authors.forename: A
authors.initials: A
authors.lastname: Shetty
authors.forename: L
authors.initials: L
authors.lastname: Xiao
authors.forename: B J
authors.initials: BJ
authors.lastname: Atkinson
authors.forename: P
authors.initials: P
authors.lastname: Corn
authors.forename: L C
authors.initials: LC
authors.lastname: Pagliaro
authors.forename: R E
authors.initials: RE
authors.lastname: Millikan
authors.forename: C
authors.initials: C
authors.lastname: Charnsangave
authors.forename: E
authors.initials: E
authors.lastname: Jonasch
authors.forename: N M
authors.initials: NM
authors.lastname: Tannir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: Angiogenesis; Mammalian target of rapamycin; Metastatic renal cell carcinoma; Pazopanib; Targeted therapy; Tyrosine kinase inhibitor